Understanding and communicating the benefits and risks of denosumab, raloxifene, and teriparatide for the treatment of osteoporosis.

The number needed to treat is a valuable metric to determine the benefit of therapy, but it must be viewed against the respective number needed to harm. Denosumab and teriparatide (TPTD) have proven antifracture efficacy at vertebral and nonvertebral sites, whereas raloxifene has proven antifracture efficacy at the spine only. Denosumab use has been associated with a small, yet statistically significant, increased incidence of eczema and serious cellulitis.

Improvements in hip trabecular, subcortical, and cortical density and mass in postmenopausal women with osteoporosis treated with denosumab.

In the FREEDOM study, denosumab treatment (60 mg every 6 months) decreased bone resorption, increased bone mineral density (BMD), and reduced new vertebral, nonvertebral, and hip fractures over 36 months in postmenopausal women with osteoporosis. In a subset of these women, hip quantitative computed tomography (QCT) was performed at baseline and months 12, 24, and 36. These scans were analyzed using Medical Image Analysis Framework (MIAF) software, which allowed assessment of total hip integral, trabecular, subcortical, and cortical compartments; the cortical compartment was further divided into 2 areas of interest (outer and inner cortex).

Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday.

The amino-bisphosphonates are first-line therapy for the treatment of most patients with osteoporosis, with proven efficacy to reduce fracture risk at the spine, hip, and other nonvertebral skeletal sites. Further, bisphosphonates have been associated with a significant decrease in morbidity and increase in survival. Following the use of bisphosphonates in millions of patients in clinical practice, some unexpected possible adverse effects have been reported, including osteonecrosis of the jaw, atypical femur fractures, atrial fibrillation, and esophageal cancer.

Denosumab densitometric changes assessed by quantitative computed tomography at the spine and hip in postmenopausal women with osteoporosis.

FREEDOM was a phase 3 trial in 7808 women aged 60-90yr with postmenopausal osteoporosis. Subjects received placebo or 60 mg denosumab subcutaneously every 6mo for 3yr in addition to daily calcium and vitamin D. Denosumab significantly decreased bone turnover; increased dual-energy X-ray absorptiometry (DXA) areal bone mineral density (aBMD); and significantly reduced new vertebral, nonvertebral, and hip fractures.

Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass.

Context: Denosumab treatment for 24 months increased bone mineral density (BMD) and reduced bone turnover markers (BTM) in postmenopausal women.

Objective: The aim was to determine the effects of prior denosumab or placebo injections on BMD, BTM, and safety over 24 months after treatment discontinuation.

Design: We conducted an off-treatment extension of a phase 3, randomized, double-blind, parallel-group study.

Assessing fracture risk and effects of osteoporosis drugs: bone mineral density and beyond.

Although there have been numerous advances in the assessment of bone strength and fracture risk, the majority of these techniques can only be performed in research laboratories, making them largely unavailable to practicing clinicians. Prospective epidemiologic studies have identified risk factors that can be assessed within the clinic and combined with bone mineral density to allow clinicians to better identify untreated individuals at heightened risk for fracture and to make informed treatment decisions based on 10-year absolute fracture risk. This article discusses the assessment of fracture risk in clinical practice, reviews currently and soon-available bone measurement tools, and details the impacts of osteoporosis therapies on fracture risk.

Bazedoxifene, a selective estrogen receptor modulator: effects on the endometrium, ovaries, and breast from a randomized controlled trial in osteoporotic postmenopausal women.

Objective: The aim of this study was to evaluate the endometrial, ovarian, and breast safety of bazedoxifene used as a treatment for postmenopausal osteoporosis.

Methods: Healthy women (aged 55-85 y) with osteoporosis were enrolled in a randomized, double-blind, placebo-controlled phase 3 trial. Participants were randomized to treatment with bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo daily for 3 years.

Effects of denosumab on bone mineral density and bone turnover in postmenopausal women.

Context: Denosumab is an investigational fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, a mediator of osteoclastogenesis and osteoclast survival.

Objective: This study evaluated the ability of denosumab to increase bone mineral density (BMD) and decrease bone turnover markers (BTMs) in early and later postmenopausal women with low BMD.

Design And Setting: This 2-yr randomized, double-blind, placebo-controlled study was conducted in North America.

Duloxetine compared with placebo for the treatment of women with mixed urinary incontinence.

Aims: Evaluate duloxetine in the treatment of women with mixed urinary incontinence (MUI).

Materials And Methods: 588 women, 19-85 years old with >or=4 incontinence episodes/week were randomly assigned to duloxetine 80 mg/day (N = 300) or placebo (N = 288). Patients were classified into three symptom subgroups: stress or urge predominant MUI (SPMUI or UPMUI) or balanced MUI (BMUI) based on their responses to the validated Stress/Urge Incontinence Questionnaire.

Canadian Consensus Conference on osteoporosis, 2006 update.

Objective: To provide guidelines for the health care provider on the diagnosis and clinical management of postmenopausal osteoporosis.

Outcomes: Strategies for identifying and evaluating high-risk individuals, the use of bone mineral density (BMD) and bone turnover markers in assessing diagnosis and response to management, and recommendations regarding nutrition, physical activity, and the selection of pharmacologic therapy to prevent and manage osteoporosis.

Evidence: MEDLINE and the Cochrane database were searched for articles in English on subjects related to osteoporosis diagnosis, prevention, and management from March 2001 to April 2005.

Validation of a two-item quantitative questionnaire for the triage of women with urinary incontinence.

Objective: To evaluate the reproducibility, construct validity, and preferences for the 2-item Stress/Urge Incontinence Questionnaire.

Methods: The questionnaire asks a patient to recall the number of stress urinary incontinence and urge urinary incontinence episodes she experienced during the preceding week. The 4-week prospective study included 3 office visits and enrolled women with stress, urge, or mixed urinary incontinence symptoms.

Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use.

All therapies currently recommended for the management of osteoporosis act mainly to inhibit bone resorption and reduce bone remodeling. PTH and its analog, teriparatide [recombinant human PTH(1-34)], represent a new class of anabolic therapies for the treatment of severe osteoporosis, having the potential to improve skeletal microarchitecture. Significant reductions in both vertebral and appendicular fracture rates have been demonstrated in the phase III trial of teriparatide, involving elderly women with at least one prevalent vertebral fracture before the onset of therapy.

Vitamin D deficiency and whole-body and femur bone mass relative to weight in healthy newborns.

Background: Vitamin D is required for normal bone growth and mineralization. We sought to determine whether vitamin D deficiency at birth is associated with bone mineral content (BMC) of Canadian infants.

Methods: We measured plasma 25-hydroxyvitamin D [25(OH)D] as an indicator of vitamin D status in 50 healthy mothers and their newborn term infants.

Osteoporosis in men: epidemiology, diagnosis, prevention, and treatment.

Background: Osteoporosis and fragility fractures in men account for substantial health care expenditures and decreased quality of life.

Objective: This article reviews the most current information about the epidemiology, diagnosis, prevention, and treatment of osteoporosis in men.

Methods: Relevant literature was identified through a search of MEDLINE (1966-June 2003) limited to English-language studies in men.

Diagnosis and management of vertebral fractures in elderly adults.

We reviewed the epidemiology, diagnosis, and treatment of vertebral fractures due to osteoporosis in the elderly. Vertebral fractures are underdiagnosed despite their high prevalence in both men and women. Clinical consequences of vertebral fractures include increased risk of future vertebral and hip fracture, acute and chronic back pain, decreased quality of life, and increased mortality.